Papillary serous carcinoma of the peritoneum (PSCP) is a malignancy, occuring exclusively in women, which is histologically indistinguishable from papillary serous carcinoma of the ovary. The disease is defined as a high grade serous adenocarcinoma with diffuse peritoneal involvement in the presence of normal sized ovaries in which the ovarian cortex is spared or minimally involved, and the ovarian stroma is not invaded. PSCP may develop years after oophorectomy for benign disease or after prophylatic oophorectomy for a family history of ovarian cancer. The occurrence of PSCP in these patients may significantly reduce the effectiveness of prophylactic oophorectomy in reducing cancer morbility. It is therefore of paramount important that one gains a better understanding of the molecular pathogenesis and the origin and of PSCP. In spite of all the studies in invasive papillary serous carcinoma of the ovary, the genetic alterations in PSCP have not been defined. Furthermore, the question of whether different peritoneal implants in PSCP arise independently from the peritoneum (i.e. multifocal in origin) remains to be answered. The establishment of the Primary Peritoneal Registry provides us with an unique opportunity to assess and collect all the PSCP cases which are available for our molecular genetic study. We propose (1). To define the pattern of loss of heterozygosity (LOH) by Southern blot analysis and PCR amplification of tandem repeats; and identify specific proto-oncogene (s) activation and tumor suppressor gene(s) inactivation in PSCP by Southern blot techniques; (2). To screen for somatic genetic alterations in PSCP by arbitrarily primed PCR (AP-PCR), isolate and perform chromosomal localization of DNA sequences representing quantitative genetic alterations in PSCP; and (3). To examine the possible multifocal in origin of peritoneal tumor implants from different sites using molecular genetic markers including X- chromosome inactivation, LOH, specific point mutation and DNA fingerprinting. These studies may serve to distinguish PSCP from epithelial ovarian cancer. A better understanding of PSCP is of clinical important in the clinical management of patients with familial ovarian cancer syndromes who are considering or have undergone prophylactic oophorectomy.